Download Chapter 5 Drug Tests: Their Uses And Limitations

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts

Neuropsychopharmacology wikipedia , lookup

Polysubstance dependence wikipedia , lookup

Neuropharmacology wikipedia , lookup

Theralizumab wikipedia , lookup

Bad Pharma wikipedia , lookup

Drug design wikipedia , lookup

Pharmacognosy wikipedia , lookup

Pharmacogenomics wikipedia , lookup

Pharmaceutical industry wikipedia , lookup

Medication wikipedia , lookup

Prescription costs wikipedia , lookup

Prescription drug prices in the United States wikipedia , lookup

Pharmacokinetics wikipedia , lookup

Drug interaction wikipedia , lookup

Drug discovery wikipedia , lookup

Transcript
C H A P T E R
5
DRUG TESTS:
S: THEIR USES AND LIMITATIONS
Introduction
In order to ascertain whether an individual has administered drugs of abuse or not, drug
testing is commonly employed to check for the presence of any drug(s) of abuse or their
metabolites in the donor’s biological specimen such as blood, urine, oral fluid, sweat or hair.
Urine has been and remains the mostly widely used body fluid specimen for routine
testing for drugs of abuse, but oral fluid, sweat and hair are gaining scientific credibility as
alternative specimens following advancement of testing technology. This chapter reviews the
uses and limitations of different specimens for testing with respect to their time window of
detection, ease of specimen collection and likelihood of adulteration.
Dr. TAM Wai Ming, Thomas
Senior Chemist,
Government Laboratory
Purposes of drug testing
Over the past several decades, drug testing has been used worldwide in a variety of
disciplines including criminal justice, emergency medicine and clinical toxicology, and
workplace [1].
Criminal justice
Drug testing plays an important role in facilitating the judicial sentence of drug abusers in
courts, drug surveillance programmes of inmates who are detained under the custody of
drug treatment centres, as well as the enforcement of the legislation of driving under the
influence by police.
Emergency medicine and clinical toxicology
Timely and reliable drug test results are of prime importance in the field of emergency
medicine and clinical toxicology. The objective of testing is focused on determining the
class of drugs that has been inadvertently or purposely ingested or exposed to the patients.
Mortalities and morbidities would then be greatly reduced by effective, appropriate and
prompt antidotal treatment or supportive care.
Workplace
Pre-employment and workplace drug testing has increased rapidly over the last decade
in western countries such as United States of America and United Kingdom. Federal
organisations, government agencies, military and private corporations exercise drug testing
either under mandatory legislation or corporate commitment as a measure to improve safety
within the workplace.
Types of specimens for testing [2]
Blood
Blood is widely used for drug testing in clinical and emergency toxicology because it offers
the best correlation between drug level and pharmacological impairments to the body. The
time window for drug detection in blood is shorter, mostly within several hours, than
in urine. For eexample, at a given dosage of cocaine, blood testing
can detect usee within 12 hours while urine testing can detect use
within 48 to 72
7 hours. Even though blood is a good specimen
for determ
mining the presence of drugs, the concerns about
in
nvasiveness of the collection, ease of transportation
aand storage, and specimen stability greatly hamper
its popularity in other fields of application even
though substitution and dilution of specimen to
tamper with drug testing are considered impossible.
Source: First Test Ltd.
31
CHAPTER
R 5 | DRUG TESTS: THEIR USES AND LIMITATIONS
Urine
By far, urine is the most widely used specimen for drugs of abuse testing
because of the advantages of large specimen volume and relatively high
drug concentrations that render drug detection comparatively easier than
in other specimens. In addition, the technology used in urine testing is
well developed and has withstood legal challenges. Furthermore, urine
collection is considered non-invasive, and specimens can be collected by
non-medical personnel. Urine is a matrix that remains stable over time
and can be frozen to maintain the integrity of the sample. Drugs in
urine are normally detectable up to 1-3 days. However, unless the
urine sample is obtained under direct observation, adulteration,
substitution or dilution to circumvent drug testing is possible.
1. Cut the hair for analysis
2. Weigh
h the hair specimen
3. Extract the hair specimen
for analysis
4. Hair specimen
spec
after
extraction
ction
5. Add extract to ELISA plate
6. ELISA
A Au
Automation
Oral fluid
Oral fluid is increasingly used for drug testing because the concentrations of many
drugs in oral fluid
d correlate well with blood concentrations. Advancement of
instru
umental sensitivity makes oral fluid a suitable alternative to
blood
d. Oral fluid is a non-invasive specimen that can be sampled
under direct observation to prevent adulteration or substitution.
The main disadvantage of oral fluid testing is its short
7. Confirmation
firma
by LCMSMS
window of detection, with most drugs being detectable
within several hours only. This characteristic renders it suitable for
w
determining very recent drug abuse, but weakens its ability in detecting
use over time. For example, someone administered heroin a day ago is
likelyy to be tested negative by oral fluid test, but positive by urine test.
Sweat
Collection of sweat is undertaken by attaching a tamper evident patch, with underlying
adsorbent pad inside, to the skin over a relatively long period of time (10-14 days). Analysis
of sweat must be performed in a laboratory and on-site test kits are not available. Sweat
testing has not widely been used because of challenges of the potential contamination from
the environment and from residual levels of drug in the skin from prior use.
32
Source: First Test Ltd.
Source: First Test Ltd.
Hair
Following the advancement of technology in
detecting trace quantity of drug(s) in hair, hair
testing has gained attention because of its ability
in providing a longer window of detection from
months to years when compared to other specimens.
In contrast to providing short-term drug abuse
profile through blood and urine testing, hair
testing provides complementar y information
about the long-term drug abuse history of a donor.
Furthermore, sampling head hair specimen is
considered non-invasive and the drugs incorporated
in the hair remain stable and bound for a long time
leading to no concern about specimen adulteration.
Head hair sampled from the scalp is preferred in
order to obtain the retrospective chronological drug
abuse history of a donor. Head hair tends to grow at
a rate of about 1 cm per month, so a 3 cm section of
hair would represent a 3 month history. However,
testing for drug in hair is comparatively time
consuming and costly, and it must be performed in
the laboratory because of unavailability of on-site
screening kits.
CHAPTER 5 | DRUG TESTS: THEIR USES AND LIMITATIONS
Characteristics of different specimens for drug testing
The advantages, disadvantages and time window of detection of different specimens are
summarised in Annex 1.
Screening test versus confirmatory test
In order to undertake drug testing, there must be a cutoff level for each type of drugs to
be tested, and such cutoff point serves as an administrative breakpoint in distinguishing a
positive or negative result. Any sample that contains the drug/drug metabolite of interest
at the concentration levels equal to or greater than the designated cutoff level is reported
as positive, whilst a negative is reported for the concentration level less than the cutoff.
Generally, a drug test can be categorised as either a screening test or a confirmatory test,
with respect to the detection method and testing principle being employed [3].
Screening test
Screening test refers to the initial test undertaken to test for a broad class of drugs and their
metabolites in the specimen with presumptive result, i.e. positive or negative. Generally
screening test is rapid, sensitive, inexpensive with acceptable levels of precision and
reliability, however, it lacks precise specificity and may be subject to a false positive result
due to cross-reactivity with other non-targeted drugs of similar chemical structure.
Immunoassay, which works on the principle of competitive interaction between the antigen
and antibody, is the common contemporary technology employed for screening tests.
Annex 1. Specimens for Drug Testing
Specimen
Advantages
Disadvantages
Window of detection
Urine
•
•
•
•
• Susceptible to adulteration or
substitution
• No dose-concentration
relationship
• Test sometimes viewed as
psychologically invasive or
embarrassing
• Biological hazard for specimen
handling and shipping to
laboratory
Typically 1 to 3 days,
except for cannabis
(1 day to 2 weeks)
Oral Fluids
• Sample obtained under direct
observation
• Minimal risk of tampering
• Non-invasive specimen collection
• Samples can be collected easily in
virtually any environment
• Reflects recent drug use
• Drugs and drug metabolites do
not remain in oral fluids as long as
they do in urine
• Less effective than other testing
methods in detecting marijuana
use
Approximately 10 to
24 hours
Hair
•
•
•
•
Longer window of detection
Greater stability (does not deteriorate)
Can measure chronic drug use
Convenient for transport and storage
(no need to refrigerate)
• Collection procedure not considered
invasive or embarrassing
• More difficult to adulterate than urine
• More expensive
• No on-site testing kit is available
• Inability to detect very recent
drug use (1 to 7 days prior to test)
Months to year
Sweat
• Non-invasive specimen collection
• Quick application and removal
• Longer window of detection than urine
(a period of days to weeks)
• No sample substitution possible
• Provides cumulative measure of drug
exposure
• Limited number of labs able to
process results
• People with skin eruptions,
excessive hair, or cuts and
abrasions cannot wear the patch
• Passive exposure to drugs may
contaminate patch and affect
results
1 to 4 weeks
Highest assurance of reliable results
Least expensive
On-site testing kits are available
Acceptable in court to withstand legal
challenge
33
CHAPTER 5 | DRUG TESTS: THEIR USES AND LIMITATIONS
On-site screening test
Use of on-site immunoassay screening kits are highly popular in the fields of workplace
testing and emergency toxicology because results are available within several minutes, with
reliability similar to laboratory screening, at the site of specimen collection. Furthermore,
these kits involve no calibration or maintenance, and no special skills are needed to perform
the screening test. Most kits have built-in quality control zones in each panel, which ensures
reagent integrity and testing validity. Nowadays, commercially-available on-site screening test
kits are usually designed for urine and saliva specimens only, but not for sweat or hair as yet.
Laboratory screening test
Instead of on-site testing, drug screening may also be performed by instrumental
immunoassay method in the laboratory by automated, sophisticated and high throughput
analysers. Laboratory screening test is privileged by its capability of processing large
numbers of samples, along with better instrumental logged quality control and integrity
assurance when compared to on-site testing.
Generally, laboratory drug screening has to take at least 1-2 days before the results are ready
for collection because of time taken in delivering the specimens to the laboratory, running
the tests and preparation of test reports.
Confirmatory testing
Any specimen, which has been presumptively screened positive, should be subject
to confirmatory testing in order to eliminate false-positive results that arise from
cross reactivity. Confirmatory testing should employ highly specific and alternate
chemical technique in order to obtain unequivocal and accurate analytical results. Gas
chromatography/mass spectrometry (GC/MS) or liquid chromatography/mass spectrometry
(LC/MS) are preferred confirmatory techniques because of their remarkable specificity and
selectivity. When compared to screening testing, confirmatory testing is time-consuming,
labour-intensive and more expensive.
Kits for on-site testing
Over the past 10 years, testing kits of different designs have been marketed in order to
meet the growing demand for drug screening at point of collection. These on-site test kits
are commonly used by healthcare professionals, and drug treatment and rehabilitation
programme supervisors to help deter drug use by the patients and supervisees, respectively.
Dipcards and cassette kits that employ lateral flow immunoassay technology have been
proven to be reliable and easy to use [4]. Recently, newly designed testing cups, also
employing the same technology, with integrated test strips in the interior surface have
grown in popularity because of their ease of testing and sanitary protection to the test
operator, with the elimination of specimen transfer or direct contact with the specimen.
Cassette
Testing cup
Source: First Test Ltd.
Dipcard
Figure 1. Different kinds of kits for on-site testing.
34
CHAPTER
R 5 | DRUG TESTS: THEIR USES AND LIMITATIONS
Adulteration of specimens to interfere with testing
Amongst the four kinds of specimens discussed, urine may be subject to adulteration in
order to circumvent drug detection. Meanwhile the chance of adulterating saliva, hair and
sweat is relatively low because these specimens may be collected under direct observation.
Adulteration and substitution of synthetic urine are the unscrupulous acts of tampering
with a urine specimen with the intention of altering the test result. Generally adulterants are
classified into three basic types :
i. Those that decrease the concentration of drugs through consuming detoxifying drinks/
pills, and/or drinking excessive amount of water prior to urine sampling;
ii. Those that decrease the drug level in urine by covertly adding a large quantity of water
soon after urine has been collected; and
iii. Those that break down the drugs or interfere with the ability of the assay through
alteration of acidity (pH) by addition of household substances or detoxifying products.
Adulterants may be either household chemicals for domestic uses or detoxifying agents that
can be purchased through the internet.
Consuming detoxifying drinks/pills and excessive quantity of water
A person may attempt to thwart a drug test by consuming detoxifying drinks/pills or
diuretics such as herbal tea, and/or drinking excessive quantity of water so that the
concentrations of drug metabolites in the urine are diluted to below detectable thresholds.
However, the donor may experience water intoxication in cases of extreme conditions.
Minimising the time duration allowed for the donor to drink fluids prior to testing is
considered the best way to deter this unscrupulous attempt. Furthermore, the
consider
unussually low creatinine and specific gravity levels in urine may serve as
ind
dicators for alertness.
D
Diluting
urine by adding in plenty of water
A negative result for the presence of abused drugs in a urine specimen
does not necessarily mean that no drug is present. It is possible that
the amount of drug is below the cut-off values used in the drug testing
protocol. Diluting urine by adding in plenty of water is the simplest way
to
o circumvent a drug test if the original concentrations of the drugs in the
urine are not substantially high. The opportunity to dilute urine samples
is miinimised by not having a source of water in the test room or the water is
coloured
d. Testing specific gravity and creatinine level remain as effective tools to
counteract this dilution tactic.
Addition of oxidising chemicals or exogenous detoxifying agents
Many chemicals are often used to adulterate urine in order to avoid a positive test result.
Bleach, hydrogen peroxide, laundry detergents, nitrite, pyridinium chlorochromate and
iodine are the common oxidising adulterants used to break down the drugs and drugs
metabolites in the urine. Also, addition of glutaraldehyde can give false negative screening
results by disrupting the enzyme used in some immunoassay tests. Alteration of pH by
addition of acid, lemon juice and vinegar is another way to interfere with the assay process.
In addition, various detoxifying agents that are easily available through internet are alleged
to be able to affect the results of a drug test after adulteration into urine samples.
Substitution by synthetic urine
Synthetic urine may be used to substitute the urine sample from a donor leading to a
negative test result if sample collection is not supervised. Synthetic urine has all the
characteristics of natural urine, with correct pH, specific gravity and creatinine level, but
with a temperature unusually low when compared to body temperature. Some urine test kits
have a built-in temperature measurement band to negate this substitution strategy, thus the
testing operator should be alerted if the sample temperature is below 32 °C.
35
CHAPTER
R 5 | DRUG TESTS: THEIR USES AND LIMITATIONS
Test strips for detecting adulterants
Source: First Test Ltd.
In order to interfere with a drug test, someone may add adulterants into the urine specimen
leading to the inability to run the test (an invalid test) or a false negative result. If the
integrity of a urine specimen is in doubt, a urine adulteration test strip should be used
to help assessment. Each test strip contains 6 to 7 chemical-treated reagent pads that will
change colour upon dipping the testing strip into the specimen. Through colour comparison,
the test strip can screen for irregularity of levels of creatinine, nitrite, glutaraldehyde, pH,
specific gravity, oxidants and pyridinium chlorochromate in the urine specimen.
References
1. Wong RC, Tse HY. Drugs of abuse – body fluid testing. USA: Humana Press, 2005.
2. Lessenger JE, Roper GF. Drugs courts – a new approach to treatment and rehabilitation. New York:
Springer Science, 2007.
3. Coombs RH. Addiction recovery tools. California: Sage Publications, 2001.
4. Lowinson JH. Substance abuse. Philadelphia: Lippincott Williams & Wilkins, 2005.
36